Fibromyalgia (FM) is a clinical state of widespread musculoskeletal pain with multiple tender points that is most common in postmenopausal women. Fatigue, particularly post-exertional, is an additional hallmark of the syndrome. FM likely has no single etiology and may have neuroendocrine, neurologic, immune and musculoskeletal components. Fatigue and fatigability also contribute directly to functional dependence and activity limitations that impact quality of life among the aged. Although associated with co-morbidities, fatigue in the elderly is often not associated with an identified medical cause. The relationship among fatigue associated with FM, fatigue associated with disease, and exacerbation of fatigue symptoms with age are unexplored. The goal of this pilot study is to identify defects in muscle physiology of older FM patients, as well as older healthy but fatigable individuals, which may contribute to this symptom. Older normal healthy women and women who are healthy but prove most fatiguable during testing, as well as older women diagnosed with FM, will be studied. Aim 1 will test the hypothesis that decreased blood flow and reduced muscle oxygenation contribute directly to pain and post exercise fatigue. Using novel, noninvasive near-infrared diffuse optical spectroscopies, muscle blood flow and oxygen saturation will be quantified before, during and after an acute bout of exercise. To identify mechanisms underlying reduced tissue oxygenation, muscle microvasculature will be analyzed in Aim 2. Vascular density and endothelial function will be assessed in muscle biopsies by immunofluorescent detection of endothelial cell antigens and detection of endothelial alkaline phosphatase, and non-invasively with the flow-mediated dilatation (FMD) test and optical probe. Aim 3 will test the hypothesis that the long term consequence of reduced muscle oxygenation may be compromised mitochondrial function. Assays of mitochondrial oxidative phosphorylation from muscle biopsies will be performed, including respiration rates and complex I-IV activities. Aberrant accumulation of mitochondrial metabolites may alter muscle vasodilatory properties, further reducing oxygen availability contributing to the pain and fatigue of FM, as well as fatigue in the elderly. PUBLIC HEALTH RELEVANCE: Fibromyalgia is increasingly common in postmenopausal women. As FM is commonly associated with pain, fatigue, sleep disturbances, depression, psychological and mood disorders, and cognitive deficiencies, individuals with FM may suffer from temporary to permanent debilitation. This project will explore the role of altered muscle physiology as a contributor to the pain and fatigue experienced by fibromyalgic patients, as well as older healthy women experiencing fatigue.